The long term goal of this section of the proposal is to examine host response factors which are potential risk factors for the development of periodontal disease and, furthermore, to identify those host response factors which are predictive for the development of periodontal disease. Based upon evidence accumulated in the past decade, we propose to investigate defects in neutrophil function as risk factors, and antibody levels in serum and saliva as predictive factors for periodontal disease. The specific aims, therefore, are: (1) to assess abnormalities of complement receptor expression on neutrophils from a large group of subjects selected by a random process, (2) to evaluate the in vitro and in vivo functional status of neutrophils in subjects with severe periodontal disease; and (3) to measure salivary and serum antibodies to candidate periodontopathic bacteria in a large group of subjects. Neutrophil receptors for the opsonic fragments of C3, namely CRl, CR2, CR3 as well as C5a, will be assessed in a group of approximately 2,500 individuals who are also examined for periodontal disease and periodontal microflora. Those with severe periodontal disease will be culled from this group and their neutrophils will be assessed for neutrophil chemotaxis. Those with severe periodontal disease exhibiting defective neutrophil chemotaxis or aberrations of surface receptors will then be studied for abnormalities in other neutrophil functions including chemotaxis through basement membranes, CR3 modulation, fibronectin binding, C3b-mediated phagocytosis, and neutrophil oxidative metabolism. In addition, these patients will be assessed for in vivo migration of gingival leukocytes in response to casein. In a parallel series of studies, salivary IgG, IgM and IgA levels; and serum and salivary antibodies to a panel of periodontal bacteria, will be assessed by ELISA. Serum antibodies from the subjects with severe periodontal disease will be evaluated every six months for two years to determine if there are fluctuations in antibody levels to periodontal pathogens which are associated with periods of periodontal destruction and healing. Based upon these studies, we should be able to determine the relative importance of neutrophils and antibodies as risk factors or predictors for the development of periodontal disease.